Multi-faceted obesity treatment demonstrates the best weight loss (WL) outcomes, yet the most effective site and methods for treatment delivery and follow-up remain elusive. Compounding the persistent treatment enigmas, aging in women is associated with an increasingly sedentary lifestyle that reduces total daily energy expenditure, predisposing to obesity. Moreover, candidate genes that contribute to the heritability of body weight and body fat distribution also may influence the response to WL treatment. In a nation with an unrelenting epidemic of obesity, the need for treatment far exceeds the capacity of the health care system to provide care on an individual basis. The purpose of this study is to: 1) assess the effects of a multi-faceted HOME-versus CENTER-based WL program on WL, CVD risk factors, and psychosocial factors; 2) determine whether a multi-faceted HOME- or CENTER-based approach more effectively leads to sustained treatment enrollment; and 3) retrospectively determine whether women with one or more variants in selected obesity-energy expenditure or insulin-sensitivity candidate genes have different outcomes post-treatment and/or at follow-up than women without a genetic predisposition. Overweight or obese (BMI 25-40 kg/m2) women (n=100) at least one year postmenopausal but < 65 years of age will be randomized to receive CENTER- or HOME-based interventions for WL that include low intensity exercise (walking). All women will receive 2 weeks of orientation to CENTER or HOME programs onsite and have baseline data collected before 6-month CENTER or HOME-based programs begin. Evaluation will be in a stable diet and exercise status post intervention, and again after 6 months maintenance at CENTER or HOME. Multivariate analyses will be used to reduce error inflation from multiple comparisons, or Bonferonni corrections will be used when multivariate analyses are not possible. With its health promotion emphasis, nursing is an ideal discipline to conduct and translate research-based, lifestyle-modification WL interventions into practice. WL interventions that postmenopausal women will accept and sustain are essential for promoting health and prevention disease during the period of major vulnerability in their lives.